Exploration of beta-arrestin isoform signaling pathways in delta opioid receptor agonist-induced convulsions.
ERK
PQR530
beta-arrestin 1
beta-arrestin 2
biased signaling
honokiol
mice
seizure
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2022
2022
Historique:
received:
07
04
2022
accepted:
13
07
2022
entrez:
5
9
2022
pubmed:
6
9
2022
medline:
6
9
2022
Statut:
epublish
Résumé
The δ-opioid receptor (δOR) has been considered as a therapeutic target in multiple neurological and neuropsychiatric disorders particularly as δOR agonists are deemed safer alternatives relative to the more abuse-liable µ-opioid receptor drugs. Clinical development of δOR agonists, however, has been challenging in part due to the seizure-inducing effects of certain δOR agonists. Especially agonists that resemble the δOR-selective agonist SNC80 have well-established convulsive activity. Close inspection suggests that many of those seizurogenic δOR agonists efficaciously recruit β-arrestin, yet surprisingly, SNC80 displays enhanced seizure activity in β-arrestin 1 knockout mice. This finding led us to hypothesize that perhaps β-arrestin 1 is protective against, whereas β-arrestin 2 is detrimental for δOR-agonist-induced seizures. To investigate our hypothesis, we characterized three different δOR agonists (SNC80, ADL5859, ARM390) in cellular assays and
Identifiants
pubmed: 36059958
doi: 10.3389/fphar.2022.914651
pii: 914651
pmc: PMC9428791
doi:
Types de publication
Journal Article
Langues
eng
Pagination
914651Subventions
Organisme : NCI NIH HHS
ID : R01 CA069202
Pays : United States
Informations de copyright
Copyright © 2022 Blaine, Miao, Yuan, Palant, Liu, Zhang and van Rijn.
Déclaration de conflit d'intérêts
RVR is currently employed as a Principal Scientist at Septerna Inc. and holds stock options in the company. RVR holds a US patent (10,954,224) describing novel delta opioid receptor agonists. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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